The recent success of gene drive mosquitoes suppressing malaria signals a new era in vector control. Yet, reliance on secreted, natural peptides poses risks of instability, host toxicity and resistance evolution. We propose synthesizing two transformative technologies to overcome these limits: generative AI for de novo peptide design and precision membrane tethering. Proof-of-concept work shows tethering antimicrobial peptides to the gut epithelium boosts potency 100-fold. Converging these approaches enables engineering of 'smart' immune barriers-AI-designed peptides optimized for stability and specificity, anchored to create impassable surfaces for pathogens. This 't-AMP' platform potentially offers a durable, fitter and broadly applicable strategy, extending rational vector engineering from mosquitoes to ticks and sandflies, revolutionizing control of multiple neglected diseases.
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Wei et al. (2026) studied this question.
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